Migraine Genetics

05 November 2004

EPIDEMIOLOGY

Tension type headache: RR 3.18 in 1 yr for first degree relative

Cluster headache:                     positive FHx in 2.3%

Migraine with aura                    RR 3.8

Migraine without aura               RR 1.9

FAMILIAL HEMIPLEGIC MIGRAINE

Autosomal dominant

Migraine with prolonged aura

Hemiparesis usually outlasts headache

Aura can also involve  impaired consciousness, fever, meningismus, vertigo, ataxia.

50% associated with Chr 19 CACNA1A mutation

            overlap syndromes

            Pure FHM:       missense mutation

            EA2:                truncating mutation

            SCA 6:             CAG expansion in CACNA1A

            CADASIL:       different portion of Chr 19 but genetically close

            Epilepsy:           rare association

            Murine model

            Tottering mice: absence & motor seizures, mild ataxia

            Leaner mouse: absence seizures, mild ataxia

30% associated with Chr 1 K channelopathy

20% locus not found

GENETIC ASSOCIATION +/- AURA

In FHM families, members with mutation but not typical phenotype ie without hemiplegia have Chr 19 mutation

EPILEPSY & MIGRAINE

Epilepsy (positive) & hemiplegia (negative) neuronal phenomenon

Reported benign infantile familial convulsion among some FHM families

Murine model

Benign occipital & benign rolandic epilepsy associated with migraines

K channelopathy for benign familial neonatal convulsions

Na channelopathy for febrile seizures & generalized epilepsy

MITOCHONDRIAL DISORDERS & MIGRAINE

MELAS patients & relatives have high prevalence of migraines

25% Japanese migraineurs have MELAS mutation vs 0% for nonmigraineurs